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Nebulized ivermectin for COVID-19 and other respiratory diseases, a proof of concept, dose-ranging study in rats.
Chaccour, Carlos; Abizanda, Gloria; Irigoyen-Barrio, Ángel; Casellas, Aina; Aldaz, Azucena; Martínez-Galán, Fernando; Hammann, Felix; Gil, Ana Gloria.
Afiliação
  • Chaccour C; ISGlobal, Hospital Clínic - Universitat de Barcelona, Rosello 132, 5ª 2ª, 08036, Barcelona, Spain. carlos.chaccour@isglobal.org.
  • Abizanda G; Ifakara Health Institute, 67501, Ifakara, United Republic of Tanzania. carlos.chaccour@isglobal.org.
  • Irigoyen-Barrio Á; Facultad de Medicina, Universidad de Navarra, 31008, Pamplona, Spain. carlos.chaccour@isglobal.org.
  • Casellas A; Centro de Investigación Médica Aplicada, 31008, Pamplona, Spain.
  • Aldaz A; Clínica Universidad de Navarra, 31008, Pamplona, Spain.
  • Martínez-Galán F; Facultad de Farmacia y Nutrición, Universidad de Navarra, 31008, Pamplona, Spain.
  • Hammann F; Drug Development Unit Universidad de Navarra, 31008, Pamplona, Spain.
  • Gil AG; ISGlobal, Hospital Clínic - Universitat de Barcelona, Rosello 132, 5ª 2ª, 08036, Barcelona, Spain.
Sci Rep ; 10(1): 17073, 2020 10 13.
Article em En | MEDLINE | ID: mdl-33051517
Ivermectin is a widely used antiparasitic drug with known efficacy against several single-strain RNA viruses. Recent data shows significant reduction of SARS-CoV-2 replication in vitro by ivermectin concentrations not achievable with safe doses orally. Inhaled therapy has been used with success for other antiparasitics. An ethanol-based ivermectin formulation was administered once to 14 rats using a nebulizer capable of delivering particles with alveolar deposition. Rats were randomly assigned into three target dosing groups, lower dose (80-90 mg/kg), higher dose (110-140 mg/kg) or ethanol vehicle only. A toxicology profile including behavioral and weight monitoring, full blood count, biochemistry, necropsy and histological examination of the lungs was conducted. The pharmacokinetic profile of ivermectin in plasma and lungs was determined in all animals. There were no relevant changes in behavior or body weight. There was a delayed elevation in muscle enzymes compatible with rhabdomyolysis, that was also seen in the control group and has been attributed to the ethanol dose which was up to 11 g/kg in some animals. There were no histological anomalies in the lungs of any rat. Male animals received a higher ivermectin dose adjusted by adipose weight and reached higher plasma concentrations than females in the same dosing group (mean Cmax 86.2 ng/ml vs. 26.2 ng/ml in the lower dose group and 152 ng/ml vs. 51.8 ng/ml in the higher dose group). All subjects had detectable ivermectin concentrations in the lungs at seven days post intervention, up to 524.3 ng/g for high-dose male and 27.3 ng/g for low-dose females. nebulized ivermectin can reach pharmacodynamic concentrations in the lung tissue of rats, additional experiments are required to assess the safety of this formulation in larger animals.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Pneumonia Viral / Ivermectina / Infecções por Coronavirus / Antiparasitários Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Pneumonia Viral / Ivermectina / Infecções por Coronavirus / Antiparasitários Idioma: En Ano de publicação: 2020 Tipo de documento: Article